The purpose of this study is to evaluate the safety, efficacy, and side effects of beta-D-2,6-diaminopurine dioxolane (DAPD) compared to DAPD plus mycophenolate mofetil (MMF) when these drugs are added to the anti-HIV treatment regimens of people infected with HIV.

Some studies have shown that DAPD and MMF can help fight HIV. However, neither DAPD nor MMF has been approved by the Food and Drug Administration for treating HIV infection. This study will help doctors decide if DAPD and MMF are good drugs for treating HIV.

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment:

56

Study Completion Date:

April 2006

Detailed Description:

The antiretroviral potency of DAPD varies among antiretroviral-experienced patients. In vitro studies indicate that the potency of DAPD can be markedly increased by the addition of MMF. Preliminary data indicate that MMF is well tolerated in patients with advanced HIV-1 disease. However, there is currently no clinical data on the activity of DAPD combined with MMF. This study will be the first to evaluate the addition of DAPD and MMF to a patient's current antiretroviral therapy.

At study entry, patients will be randomly assigned to one of two blinded treatment arms. Arm A receives DAPD plus MMF placebo in addition to their current regimen, while Arm B receives DAPD plus MMF in addition to their current regimen. All patients remain on their current antiretroviral regimen through Week 2. After Week 2, patients who virologically respond are encouraged to remain on blinded study treatment through Week 24. Patients who do not virologically respond are unblinded.

After unblinding, patients who were not receiving MMF may add it to their antiretroviral regimen. Response to the addition of open-label MMF is assessed after 2 weeks. Resistance to antiretroviral agents, including DAPD, will be assessed following any virologic failure occurring after Week 2. All patients have the option of optimizing their background antiretroviral regimen at Week 2, based on the results of a pre-entry resistance assay; enfuvirtide will be made available for background therapy optimization through Week 48.

Patients who are still receiving DAPD alone or DAPD plus MMF at Week 48 and who are still responding virologically may choose to continue the study drug(s) and be followed for up to an additional 48 weeks. Throughout the study, HIV-1 RNA levels, CD4 cell counts, and study drug levels will be monitored regularly. Eye exams will be done at several study visits. Only DAPD, MMF, and MMF placebo will be supplied by this study; patients must obtain the rest of their treatment regimen through their doctor. Patients who discontinue treatment before the end of study will need to come in for a follow-up visit 4 weeks after discontinuation and may need to attend future follow-up visits at 8-week intervals, as determined by the investigator.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria for Step 1:

HIV infected

Triple-class antiretroviral treatment, as determined by the site investigator and as defined by all of the following: a) exposure to 2 or more nucleotide reverse transcriptase inhibitors (NRTIs) for at least 3 months each; b) exposure to 2 or more non-boosted protease inhibitors (PIs) for at least 3 months each, or exposure to a dual PI regimen for at least 3 months; and c) exposure to at least 1 non-nucleotide reverse transcriptase inhibitor (NNRTI) for at least 3 months.

CD4 cell count of at least 50 cells/mm3 within 45 days prior to study entry

Viral load of 2000 copies/ml or more within 45 days prior to study entry

On current antiretroviral treatment regimen for at least 30 days prior to study entry. If current treatment includes abacavir, abacavir must be discontinued at least 30 days prior to study entry.

Willing to use acceptable methods of contraception

Exclusion Criteria for Step 1:

Pregnant or breastfeeding

Allergy or sensitivity to the study drugs and their formulations

Diabetes mellitus

Cataracts or any measurable loss of vision due to lens opacity

Best-corrected visual acuity worse than 20/200

Certain drugs or vaccines within 30 days prior to study entry

History of any of the following: kidney disease; serious illness within 14 days prior to study entry; end organ cytomegalovirus infection; Kaposi's sarcoma; cataracts; active herpetic infection or peptic ulcer disease within 12 months; or malabsorption, severe chronic diarrhea, or inability to eat 1 or more meals a day because of chronic nausea, emesis, or abdominal/mouth and throat discomfort

Current alcohol or drug abuse that would interfere with adherence to study requirements

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00038272